Ketotifen is marketed throughout the world as an antiallergy
drug, but whether it affects infiltration of inflammatory cells into airway mucosa is not known. We studied the effects of
ketotifen on symptoms, pulmonary function, and airway
inflammation in 25 patients with atopic
asthma. Patients took
ketotifen (1 mg twice daily) or a matching placebo for 8 weeks in a double-blind, parallel-group study. Data recorded on diary cards were used for 2 weeks before treatment began, and they were used for the last 2 weeks of treatment to study
asthma symptoms, use of beta 2-agonists, and peak expiratory flow (PEF). Pulmonary function tests, bronchial responsiveness to
methacholine, and fiberoptic bronchoscopy were performed before and
after treatment. Biopsy specimens were obtained by bronchoscopy. Specimens were stained immunohistochemically with
monoclonal antibodies against stored
eosinophil cationic protein (EG1), the secreted form of
eosinophil cationic protein (EG2),
mast-cell tryptase (AA1),
neutrophil elastase (NP57), CD3, CD4, CD8, and CD25. The numbers of positively stained cells in the lamina propria were counted. Compared with the placebo, the
ketotifen-treated group exhibited significant improvement of
asthma symptoms (P < 0.05) and bronchial responsiveness (P < 0.05). This was accompanied by a reduction of EG2+ eosinophils (P < 0.05), CD3+ T cells (P < 0.001), CD4+ T cells (P < 0.01), and CD25+ activated T cells (P < 0.01) in the bronchial mucosa. These results suggested that the beneficial effects of
ketotifen in
bronchial asthma may result from consequent inhibition of activated eosinophils and T-cell recruitment into the airway. Moreover,
ketotifen may relieve allergic
inflammation in
bronchial asthma.